1bey
ANTIBODY TO CAMPATH-1H HUMANIZED FAB
|
OverviewOverview
The CAMPATH-1 family of antibodies are able systematically to lyse human, lymphocytes with human complement by targeting the small cell-surface, glycoprotein CD52, commonly called the CAMPATH-1 antigen. These antibodies, have been used clinically for several years, providing therapy for, patients with a variety of immunologically mediated diseases. We report, here the first X-ray crystallographic analyses of a Fab fragment from a, rat antibody, the original therapeutic monoclonal CAMPATH-1G and its, humanized counterpart CAMPATH-1H, into which the six, complementarity-determining regions of the rat antibody have been, introduced. These structures have been refined at 2.6 A and 3.25 A, resolution, respectively. The VL domains of adjacent molecules of, CAMPATH-1H form a symmetric dimer within the crystals with an, inter-molecular extended beta-sheet as seen in light chain dimers of the, kappa class. Crystals of CAMPATH-1G have translational pseudo-symmetry., Within the antibody-combining sites, which are dominated by the protrusion, of LysH52b and LysH53 from hypervariable loop H2, the charge distribution, and overall integrity are highly conserved, but large changes in the, position of loop H1 are observed and an altered conformation of loop H2., The major determinants of this are framework residues H71 and H24, whose, identity differs in these two antibodies. These structures provide a, detailed structural insight into the transplantation of an intact, antibody-combining site between a rodent and a human framework, and, provide an increased understanding of the specificity and antigen affinity, of this pair of CAMPATH-1 antibodies for CD52. This study forms the, structural basis for future modification and design of more effective, antibodies to this important antigen.
About this StructureAbout this Structure
1BEY is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of a rat anti-CD52 (CAMPATH-1) therapeutic antibody Fab fragment and its humanized counterpart., Cheetham GM, Hale G, Waldmann H, Bloomer AC, J Mol Biol. 1998 Nov 20;284(1):85-99. PMID:9811544
Page seeded by OCA on Sun Nov 18 09:26:30 2007